Gas Dynamic Virtual Nozzle Sprayer for an Introduction of Liquid Samples in Atmospheric Pressure Ionization Mass Spectrometry

Electrospray may exhibit inadequate ionization efficiency in some applications. In such cases, atmospheric-pressure chemical ionization (APCI) and photoionization (APPI) can be used. Despite a wide application potential, no APCI and APPI sources dedicated to very low sample flow rates exist on the market. Since the ion source performance depends on the transfer of analytes from the liquid to the gas phase, a nebulizer is a critical component of an ion source. Here, we report on the nebulizer with a gas dynamic virtual nozzle (GDVN) and its applicability in APCI at microliter-per-minute flow rates. Nebulizers differing by geometrical parameters were fabricated and characterized regarding the jet breakup regime, droplet size, droplet velocity, and spray angle for liquid flow rates of 0.75–15.0 μL/min. A micro-APCI source with the GDVN nebulizer behaved as a mass-flow-sensitive detector and provided stable and intense analyte signals. Compared to a classical APCI source, an order of magnitude lower detection limit for verapamil was achieved. Mass spectra recorded with the nebulizer in dripping and jetting modes were almost identical and did not differ from normal APCI spectra. Clogging never occurred during the experiments, indicating the high robustness of the nebulizer. Low-flow-rate APCI and APPI sources with a GDVN sprayer promise new applications for low- and medium-polar analytes.

Since it has proven difficult to reproducibly fabricate the outer glass housing with a defined exit channel diameter, we tested several fabrication approaches. The initial experiments were performed with laboratory gas and alcohol burners which mostly provided glass housing orifices with poor symmetry along the tube axis and unpredictable exit channel diameter. The glass tube was then fixed in a cordless drill chuck to control heat transfer better. Slow and even rotation (about 600 rpm) helped to improve the orifice shape, but the reproducibility was still limited by flame instability. Replacing the flame with a small, in-house resistance-heated furnace did not help much. The best results were achieved with a micropipette puller allowing precise control of the applied heat. GDVN outer housing units were fabricated using micropipette puller P-100 (Sutter Instrument, Novato, CA) equipped with a 4.5 mm wide box filament. The operating parameters of the micropipette puller were as follows: heat = 900; pull = 0; vel = any positive value; pressure = 500. While heated, the tube was rotated about its axis to fabricate radially symmetric channels.
The exit channels of 47 -320 µm I.D. were obtained by heating the tube for various lengths of time. For instance, about 15 seconds were required to achieve a 50 µm channel. A scanning electron microscope (SEM) Nova NanoSEM 450 (Thermo Fisher Scientific, San Jose, CA) showed a smooth surface and circular shape of the glass tube orifice.
Since SEM required shortening the tube and thus destroying the outer housing, an optical microscope AM7915MZT from Dino-Lite (Los Angeles, CA) was used for routine determination of the exit channel diameters. The optical microscope was also used during the assembly of the nebulizers. The tapered-tip capillary was centered inside the borosilicate glass housing tube using Electron micrograph; a view into the mouth of the outlet channel in the outer glass housing.

Supporting Information
S3 an in-house made gas permeable spacer. The spacer made from an aluminum alloy (EN-AW 6060) was a small element of triangular shape with an opening for a 365 µm fused silica capillary.

Text S2: Calculations of the droplet volume
The droplet volume was calculated according to the equation Supporting Information S4 respectively. The tip of the corona discharge electrode was positioned 5.0 mm from the mass spectrometry inlet, a distance that guaranteed maximum verapamil signal and no electric sparks.
The signal of verapamil decreased with the increasing distance between the nebulizer and the discharge electrode tip. Adjusting the correct position of the nebulizer relative to the mass spectrometer inlet proved easier for the jetting mode, likely due to the larger spray diameter. The nebulizer efficiency, especially in the jetting mode, was high, making it possible to transfer the non-volatile analyte (verapamil) into the gas phase, even without heating. The optimum nebulizer position was 2.0 mm from the discharge needle in both jet breakup regimes.     The compounds were dissolved in toluene. Spectra were recorded at a sample flow rate of 1.5 µl/min, a gas flow rate of 180 ml/min for jetting mode, and 50 ml/min for dripping mode. All mass spectra were averaged from 1-min records. Table S1.
The physical properties of solvents SI1-SI3 and the size of droplets produced by the N5 nebulizer in a dripping mode at a liquid flow rate of 5.0 µl/min and gas flow rate of 150 ml/min. The size of droplets is controlled by a combined effect of the solvents' physico-chemical properties. Viscosity tends to dampen the perturbations and stabilize droplets' growth but has little effect on droplet size SI4 . In contrast, surface tension affects the droplet volume, hence the time of break up and the shape of the jet. Surface tension increases the cohesion between the fluid elements at the droplet surface and competes against the deformation forces for the system's equilibrium.
Therefore, the greater the surface tension, the more fluid comes into the drop, and a bigger drop is formed SI5 . The droplet size also increases with the liquid density SI6, SI7 .
SI3. Surface Tension of Acetonitrile from Dortmund Data Bank.